**Clinical Response and Changes of Cytokines and Zonulin Levels in Patients with Diarrhoea-Predominant Irritable Bowel Syndrome Treated with** *Bifidobacterium Longum* **ES1 for 8 or 12 Weeks: A Preliminary Report**

**Gian Paolo Caviglia 1,\* Alessandra Tucci 2, Rinaldo Pellicano 2 Sharmila Fagoonee 3 Chiara Rosso 1, Maria Lorena Abate 1, Antonella Olivero 1 Angelo Armandi 2, Ester Vanni 2, Giorgio Maria Saracco 1 Elisabetta Bugianesi 1, Marco Astegiano 2 and Davide Giuseppe Ribaldone 1,\***


Received: 16 June 2020; Accepted: 22 July 2020; Published: 23 July 2020

**Abstract:** *Bifidobacterium longum* (*B. longum*) ES1 is a probiotic strain capable of modulating microbiome composition, anti-inflammatory activity and intestinal barrier function. We investigated the use of *B. Longum* ES1 in the treatment of patients with diarrhoea-predominant irritable bowel syndrome (IBS-D). Sixteen patients were treated for 8 or 12 weeks with *B. Longum* ES1 (1 × 10<sup>9</sup> CFU/day). Serum zonulin and cytokines were measured at baseline (T0) and at the end of therapy (T1). Clinical response to therapy was assessed by IBS Severity Scoring System. Interleukin (IL)-6, IL-8, IL-12p70 and tumor necrosis factor (TNF) α levels decreased from T0 to T1, irrespective of treatment duration (*p* < 0.05), while zonulin levels diminished only in patients treated for 12 weeks (*p* = 0.036). Clinical response was observed in 5/16 patients (31%): 4/8 (50%) treated for 12 weeks and 1/8 (13%) treated for 8 weeks. Abdominal pain improved only in patients treated for 12 weeks (5/8 vs. 0/8, *p* = 0.025), while stool consistency improved regardless of therapy duration (*p* < 0.001). In conclusion, the results of this pilot study showed, in IBS-D patients treated for 12 weeks with *B. longum* ES1, a reduction in the levels of pro-inflammatory cytokines, and intestinal permeability as well as an improvement in gastrointestinal symptoms, but further studies including a placebo-control group are necessary to prove a causal link.

**Keywords:** IBS; IL-6; IL-8; IL-12p70; intestinal permeability; zonulin
